Abstract

Drug-induced liver injury (DILI) is the most common clinical adverse drug reaction, which is closely associated with the oxidative stress caused by overproduced reactive oxygen species. Hepatic H2O2, as an important biomarker of DILI, plays a crucial role in the progression of DILI. However, there remains a challenge to develop H2O2-activatable second near-infrared (NIR-II, 1000-1700 nm) small molecular probes with both a large Stokes shift and a long emission wavelength beyond 950 nm. Herein, we developed an activatable NIR-II fluorescent probe (IR-990) with an acceptor-π-acceptor (A-π-A) skeleton for real-time detection of H2O2 in vivo. In the presence of H2O2, nonfluorescent probe IR-990 was successfully unlocked by generating a donor-π-acceptor (D-π-A) structure and switched on intense NIR-II fluorescence, exhibiting a peak emission wavelength at 990 nm and a large Stokes shift of 200 nm. Moreover, it was able to detect H2O2 with high sensitivity and selectivity in vitro (LOD = 0.59 μM) and monitor the behavior of endogenous H2O2 in the HepG2 cell model of DILI for the first time. Notably, probe IR-990 was successfully applied in real-time imaging of endogenous H2O2 generation in the DILI mouse model, showing a high signal-to-background ratio of 11.3/1. We envision that IR-990 holds great potential as a powerful diagnosis tool for real-time visualization of H2O2 in vivo and revealing the mechanism of DILI in the future.

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